Project Summary/Abstract Most of the deaths from drug overdoses are driven by synthetic opioids. Dentistry highly contributes to the opiate addiction epidemic. Following dental surgery, 85% of oral surgeons prescribe opiates, and most opiates are prescribed after wisdom teeth extraction (third molar) to reduce pain caused by dry sockets. Approximately 21 million surgical tooth extractions are performed on ~10 million patients each year in the US. Currently, different medicaments and carrier systems are commercially available to treat these patients with little scientific evidence to guide the selection process for their use Therefore, the use of opiates for pain management unfortunately continues to be the go-to treatment of choice for oral surgeons. The goal of this STTR Phase I proposal is to develop a local treatment for pain associated with the extraction of teeth, such as third molars (`wisdom teeth') that does not involve an opiate. Arcato has a history of commercializing products to serve specialty oral healthcare practitioners, such as orthodontists and oral surgeons. Arcato's first product, a combination product named OraWax?, targets orthodontists and their patients with an effective treatment for oral mucosal discomfort caused by braces. OraWax is a patented time-release formulation combining wax (a non-resorbable matrix), benzocaine, and selected polymers. The innovation of this current STTR proposal is the formulation of a resorbable matrix containing an anesthetic agent that can be placed in a tooth socket following extraction with the goal of delivering the anesthetic in a sustained release manner over a period of 4- 7 days. The Aims of this proposal are designed to reduce opiate use in patients with acute postoperative dental pain by providing an effective treatment that does not subject them to the risk of opioid addiction or the systemic toxicities of opiates and nonsteroidal anti-inflammatory analgesics (NSAIDs). In Aim 1, we will employ a Design of Experiment (DOE) approach to yield an optimized resorbable matrix containing benzocaine, lidocaine or bupivacaine. The matrix will be comprised of poloxamer-type co-polymers, surfactants and co- surfactants that slowly erode, thus allowing for the sustained release of the anesthetic agent after implantation in an alveolar socket. The selection of the prototyes to be advanced for in vivo evaluation will be based on in vitro drug release rate and rheometry of the matrix. Aim 2 will assess resorbability of the selected anesthetic- containing matrices in an alveolar extraction socket animal model. Resorption will be assessed by recovering and weighing residual matrices 7 days after implantation; micro-CT imaging and histological analysis will be used to assess if the implantation of the matrices results in bone loss or inflammation. We expect that successful development of this product and its implementation in dentistry/oral surgery practice will lead to a significant reduction in the number of opiate prescriptions written for patients suffering from dry sockets or other painful sequelae resulting from dental procedures. Furthermore, the proposed technology is potentially applicable to other situations involving skeletal bleeding and pain, e.g., following thoracic surgery.